Hypoxia-inducible factor 1alpha (HIF-1alpha), which transactivates a variety of hypoxia-induced genes, is rapidly degraded under nomoxia through the hydroxylation-ubiquitination-proteasome pathway. In this study, we addressed how HIF-1alpha is stabilized by proteasome inhibitors. The ubiquitin pool was rapidly reduced after proteasome inhibition, followed by the accumulation of non-ubiquitinated HIF-1alpha. The poly-ubiquitination of HIF-1alpha was resumed by restoration of free ubiquitin, which suggests that the HIF-1alpha stabilization under proteasome inhibition is attributed to depletion of the free ubiquitin pool. Ni2+ and Zn2+ also stabilized HIF-1alpha with depletion of the free ubiquitin pool and these effects of metal ions were attenuated by restoration of free ubiquitin. Ni2+ and Zn2+ may disturb the recycling of free ubiquitin, as MG132 does. Based on these results, the state of the ubiquitin pool seems to be another critical factor determining the cellular level of HIF-1alpha.
Cell Hypoxia/physiology ; Cell Line, Tumor ; HCT116 Cells ; HEK293 Cells ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/biosynthesis/*metabolism ; Leupeptins/pharmacology ; Nickel/chemistry ; Proteasome Endopeptidase Complex/*metabolism ; Proteasome Inhibitors/*pharmacology ; Ubiquitin/*metabolism ; Ubiquitination/*physiology ; Up-Regulation ; Zinc/chemistry

BACKGROUND: Posttraumatic stress symptoms (PTSS) in patients with psychological trauma lead to poor health-related quality of life. Understanding of the relationships among PTSS, anxiety, depression, and illness intrusiveness will guide the development of efficient approaches to enhance subjective well-being in patients with psychological trauma. This study investigated whether anxiety and depression mediate the relationship between PTSS and illness intrusiveness in the hope of providing more comprehensive and effective trauma treatment. METHODS: Psychiatric outpatients who visited the trauma clinic of a university hospital (n = 260) participated in this study. Assessments were conducted for PTSS, anxiety, depression, and illness intrusiveness. Structural equation modeling and path analysis were performed to analyze the mediating effects of anxiety and depression on the relationship between PTSS and illness intrusiveness. RESULTS: PTSS had both direct and indirect exacerbating effects on illness intrusiveness. Anxiety exhibited the largest direct exacerbating effect on illness intrusiveness. The indirect effects of PTSS on illness intrusiveness through anxiety alone and through a depression-to-anxiety pathway were significant, but the indirect effect through depression alone was not. CONCLUSION: The findings demonstrate that anxiety, both independently and as part of an interrelated pathway with depression, partially mediates the relationship between PTSS and illness intrusiveness. Appropriate interventions and a comprehensive approach to alleviate anxiety and depression could mitigate the negative effects of PTSS on illness intrusiveness in patients with psychological trauma.
Anxiety* ; Depression* ; Hope ; Humans ; Negotiating* ; Outpatients ; Psychological Trauma ; Quality of Life

BACKGROUND/AIMS: The clinical implications of hypocholesterolemia have not been well studied, although some studies have revealed an association between hypocholesterolemia and intracerebral hemorrhage (ICH). We evaluated the clinical characteristics of subjects with very low-density lipoprotein cholesterol (LDL-C) and compared the risk for ICH using various clinical parameters. METHODS: Using hospital records, we evaluated the clinical characteristics of subjects with LDL-C levels < or = 40 mg/dL (very low LDL-C group). We also evaluated the risk for ICH in this very low LDL-C group and in subjects with low LDL-C < or = 70 mg/dL (low LDL-C group). RESULTS: Among 34,415 subjects who presented at the laboratory for serum LDL-C measurements, 250 subjects had a very low serum LDL-C level (< or = 40 mg/dL). About half of the subjects were statin users; the very low LDL levels in the other subjects were likely attributable to alcohol consumption or a various chronic illness such as liver disease or end-stage renal disease (ESRD). ICH occurred in three subjects with very low LDL-C, all of whom had no history of statin use. ESRD tended to be associated with ICH in subjects with serum LDL-C < or = 70 mg/dL. CONCLUSIONS: About 1% of the subjects whose LDL-C was measured in the hospital had a LDL-C level < or = 40 mg/dL, and about half of these subjects had no history of hypolipidemic therapy. ICH incidence was not related to LDL-C level or statin use.
Aged ; Alcohol Drinking/adverse effects/epidemiology ; Biological Markers/blood ; Cerebral Hemorrhage/blood/*epidemiology ; Cholesterol, LDL/*blood ; Down-Regulation ; Dyslipidemias/blood/*epidemiology ; Female ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects ; Incidence ; Kidney Failure, Chronic/epidemiology ; Liver Diseases/epidemiology ; Male ; Middle Aged ; Republic of Korea/epidemiology ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Time Factors